title: CYP1A1 genetic polymorphism and polycyclic aromatic hydrocarbons on pulmonary function in the elderly: haplotype-based approach for gene-environment interaction.
abstract: Lung function may be impaired by environmental pollutants not only acting alone, but working with genetic factors as well. Few epidemiologic studies have been conducted to explore the interplay of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic polymorphism on lung function in the elderly. For genetic polymorphism, haplotype is considered a more informative unit than single nucleotide polymorphism markers. Therefore, we examined the role of haplotype based-CYP1A1 polymorphism in the effect of PAHs exposure on lung function in 422 participants from a community-based panel of elderly adults in Seoul, Korea. Linear mixed effect models were fit to evaluate the association of PAH exposure markers (urinary 1-hydroxypyrene and 2-naphthol) with FVC, FEV₁, FEV₁/FVC, and FEF₂₅₋₇₅, and then the interaction with CYP1A1 haplotype constructed from three single nucleotide polymorphisms of the gene (rs4646421/rs4646422/rs1048943). Urinary 1-hydroxypyrene levels were inversely associated with FEV₁/FVC (p<0.05), whereas urinary 2-naphthol levels failed to show associations with lung function. Urinary 1-hydroxypyrene was significantly associated with decrease in FEV₁/FVC among participants with rs4646421 variants (CT+TT), rs4646422 wild-type (GG), and rs1048943 wild-type (AA). At least one TGA haplotype predicted a 0.88% (95% confidence interval, 0.31-1.45%) reduction in FEV₁/FVC with an interquartile range increase in 1-hydroxypyrene, whereas no relationship was observed in participants without TGA haplotype (p for interaction=0.045). Similar patterns were also observed in FEF₂₅₋₇₅. We did not find any main effects of CYP1A1 genetic polymorphisms on lung functions. Our findings suggest that PAH exposure producing 1-hydroxypyrene as a metabolite compromises lung function in the elderly, and that haplotype-based CYP1A1 polymorphism modifies the risk.
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Yoon-Hyeong
authors.initials: YH
authors.lastname: Choi
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Yun-Chul
authors.initials: YC
authors.lastname: Hong
mesh_terms: D000368:Aged; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009284:Naphthols / Q000652:urine; D011084:Polycyclic Aromatic Hydrocarbons / Q000493:pharmacokinetics / Q000506:poisoning*; D020641:Polymorphism, Single Nucleotide; D011721:Pyrenes / Q000652:urine; D060888:Real-Time Polymerase Chain Reaction; D056910:Republic of Korea; D012129:Respiratory Function Tests
chemical_list: D009284:Naphthols; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D004247:DNA; D019363:Cytochrome P-450 CYP1A1; C033146:1-hydroxypyrene; C028405:2-naphthol
keywords: 1-OHP; 1-hydroxypyrene; BMI; CI; Cytochrome P-450 1A1; Epidemiology; FEF(25–75); FEV(1); FVC; GST; Gene–environment interaction; Haplotypes; IQR; KEEP; Korean elderly environmental panel; LOD; Lung; PAH; Polycyclic aromatic hydrocarbons; SD; SNP; body mass index; confidence interval; forced expiratory flow between 25% and 75% of the FVC; forced expiratory volume in one second; forced vital capacity; glutathione S-transferase; interquartile range; limits of detection; polycyclic aromatic hydrocarbon; single polymorphism; standard deviation